Background

Hyperthermic intraperitoneal chemotherapy (HIPEC) at interval cytoreductive surgery for ovarian cancer improves overall survival but its role in recurrent disease is uncertain. We aimed to compare outcomes in patients treated with or without HIPEC during surgery for recurrent ovarian cancer.

Methods

The multicentre, open-label, randomised, phase 3 CHIPOR trial was conducted at 31 sites in France, Belgium, Spain, and Canada, and enrolled patients with first relapse of epithelial ovarian cancer at least 6 months after completing platinum-based chemotherapy. Eligible patients were aged 18 years or older with WHO performance status of less than 2. After six cycles of platinum-based chemotherapy (and optional bevacizumab), patients amenable to complete cytoreductive surgery were randomly assigned centrally in a 1:1 ratio, using a web-based system and a minimisation procedure, during surgery to receive HIPEC (cisplatin 75 mg/m² in 2 L/m² of serum at 41±1°C for 60 min) or not, stratified by centre, completeness of cytoreduction score, platinum-free interval, and latterly, planned poly(ADP-ribose) polymerase inhibitor use. The primary endpoint was overall survival, analysed on an intention-to-treat basis in all randomly assigned patients. This ongoing trial is registered with ClinicalTrials.gov, NCT01376752.

Findings

Between May 11, 2011, and May 14, 2021, 415 female patients were randomly assigned (207 HIPEC, 208 no HIPEC). At the primary analysis (median follow-up 6·2 years, IQR 4·1–8·1), 268 (65%) patients had died (126 [61%] of 207 in the HIPEC group; 142 [68%] of 208 in the no-HIPEC group). Overall survival was significantly improved with HIPEC (stratified hazard ratio 0·73, 95% CI 0·56–0·96; p=0·024). Median overall survival was 54·3 months (95% CI 41·9–61·7) with HIPEC versus 45·8 months (38·9–54·2) without. Grade 3 or worse adverse events within 60 days after surgery occurred in 102 (49%) of 207 patients receiving HIPEC versus 56 (27%) of 208 receiving no HIPEC, the most common being anaemia (47 [23%] vs 30 [14%]), hepatotoxicity (23 [11%] vs 18 [9%]), electrolyte disturbance (28 [14%] vs two [1%]), and renal failure (20 [10%] vs three [1%]). There were three deaths within 60 days of surgery, all in the no-HIPEC group.

Interpretation

Adding HIPEC to cytoreductive surgery after response to platinum-based chemotherapy at first epithelial ovarian cancer recurrence significantly improved overall survival. When treating patients with late first relapse of high-grade serous or high-grade endometrioid ovarian cancer amenable to complete cytoreductive surgery at specialist centres, platinum-based HIPEC should be considered to extend overall survival.

Funding

French National Cancer Institute and French League Against Cancer.

中文翻译：

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复发性卵巢癌的腹腔热灌注化疗 （CHIPOR）：一项随机、开放标签、3 期试验

 背景

卵巢癌的间隔性细胞减灭术腹腔热灌注化疗 （HIPEC） 可提高总生存期，但其在复发性疾病中的作用尚不确定。我们旨在比较复发性卵巢癌手术期间接受或不接受 HIPEC 治疗的患者的结局。

 方法

多中心、开放标签、随机、3 期 CHIPOR 试验在法国、比利时、西班牙和加拿大的 31 个地点进行，并招募了在完成铂类化疗后至少 6 个月首次复发的上皮性卵巢癌患者。符合条件的患者年龄在 18 岁或以上，且 WHO 体能状态小于 2。在六个周期的铂类化疗（和可选的贝伐珠单抗）后，适合完成细胞减灭术的患者以 1：1 的比例随机分配，使用基于网络的系统和最小化程序，在手术期间接受 HIPEC（顺铂 75 mg/m² 在 2 L/m² 血清中，在 41±1°C 下，持续 60 分钟）或不接受， 按中心、细胞减灭评分的完整性、无铂间隔以及后来计划使用聚（ADP-核糖）聚合酶抑制剂进行分层。主要终点是总生存期，在所有随机分配的患者的意向治疗基础上进行分析。这项正在进行的试验已在 ClinicalTrials.gov NCT01376752注册。

 发现

在 2011 年 5 月 11 日至 2021 年 5 月 14 日期间，随机分配了 415 名女性患者 （207 名 HIPEC，208 名无 HIPEC）。在初步分析中（中位随访 6·2 年，IQR 4·1-8·1），268 例 （65%） 患者死亡（HIPEC 组 207 例中的 126 例 [61%];无 HIPEC 组 208 例中的 142 例 [68%]）。HIPEC 显著提高了总生存期（分层风险比 0·73,95% CI 0·56–0·96;p=0·024）。使用 HIPEC 的中位总生存期为 54·3 个月 （95% CI 41·9–61·7），而没有 HIPEC 的中位总生存期为 45·8 个月 （38·9–54·2）。术后 60 天内 3 级或更严重的不良事件发生在 207 名接受 HIPEC 的患者中，有 102 名 （49%） 发生，而 208 名未接受 HIPEC 的患者中有 56 名 （27%） 发生，最常见的是贫血（47 [23%] 对 30 [14%]）、肝毒性（23 [11%] 对 18 [9%]）、电解质紊乱（28 [14%] 对 2 [1%]）和肾功能衰竭（20 [10%] 对 3 [1%]）。手术后 60 天内有 3 例死亡，均在无 HIPEC 组中。

 解释

在首次上皮性卵巢癌复发时对铂类化疗有反应后，在细胞减灭术中加入 HIPEC 可显著提高总生存期。当治疗适合在专科中心完成细胞减灭手术的高级别浆液性或高级别子宫内膜样卵巢癌的晚期首次复发患者时，应考虑以铂类为基础的 HIPEC 以延长总生存期。

 资金

法国国家癌症研究所和法国抗癌联盟。